Inherited Risk Factors for Chronic Lung Disease

Abstract

Laurel and Ericksson's 1 Laurel CB Eriksson S The electrophoretic A1-globulin pattern of serum in A1-antitrypsin deficiency. Scand J Clin Lab Invest. 1963; 15: 132-140 Crossref Scopus (1271) Google Scholar serendipitous discovery that severe antitrypsin deficiency is a risk factor for chronic obstructive pulmonary disease (COPD) has been well validated. Approximately ten years ago, Lieberman, 2 Lieberman J Frequency of heterozygous and homozygous alpha1-antitrypsin deficiencies in patients with pulmonary emphysema. Clin Res. 1969; 17: 165 Google Scholar Lieberman and Mittman, 3 Lieberman J Mittman C Schneider AS Screening for homozygous and heterozygous alpha1-antitrypsin deficiency. JAMA. 1969; 210: 2055 Crossref PubMed Scopus (41) Google Scholar Kueppers 4 Kueppers F Fallat R Larson RK Obstructive lung disease and alpha1-antitrypsin deficiency gene heterozygosity. Science. 1969; : 165-899 Google Scholar and others suggested that intermediate antitrypsin deficiency (PiMZ) might also be a significant risk factor for developing COPD. This factor is of great potential significance since it is found in approximately 3 percent of some populations. It is now well established that the PiMZ type occurs more often than expected in groups of patients with obstructive lung disease. 5 Mittman C The PiMZ phenotype: Is it a significant risk factor for the development of chronic obstructive lung disease?. Am Rev Respir Dis. 1978; 118: 649-652 Crossref PubMed Scopus (28) Google Scholar However, the question remains controversial since some investigators, such as Lebowitz and associates, 6 Lebowitz MD Knudsen RJ Morse JO et al. Closing volume and flow abnormalities in alpha 1-antitrypsin phenotype groups in a community population. Am Rev Respir Dis. 1978; 117: 179 PubMed Google Scholar Webb and associates 7 Webb DR Hyde RW Schwartz RH et al. Serum alpha1-antitrypsin variants: Prevalence and clinical spirometry. Am Rev Respir Dis. 1973; 108: 918 PubMed Google Scholar and others have reported that lung function tests in community populations show no differences between subjects with the PiM (normals) and variant phenotypes. Others, such as Klayton et al, 8 Klayton R Fallat R Cokes AB Determinants of chronic obstructive pulmonary disease in patients with intermediate levels of alpha1-antitrypsin. Am Rev Respir Dis. 1975; 112: 71 PubMed Google Scholar Cox and associates, 9 Cox DW Hoeppner VH Levison H Protease inhibitors in patients with chronic obstructive pulmonary disease: The alpha1-antitrypsin heterozygote controversy. Am Rev Respir Dis. 1976; 113: 601 PubMed Google Scholar and Cooper and colleagues,10 who performed studies in selected and healthy volunteers, have supported our earlier hypothesis.